Prospective associations of triglyceride-glucose related indices with cardiovascular disease and mortality in individuals with metabolic syndrome: evidence from the UK biobank.

backgroundTriglyceride‒glucose (TyG) related indices have been implicated in metabolic syndrome (MetS), cardiovascular disease (CVD), and mortality. However, their prospective associations with CVD and mortality among individuals with MetS remain limited.

methodsIn this large-scale prospective study, we included 113,699 UK Biobank participants with MetS who were free of CVD at baseline. The TyG index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), and TyG-waist-to-height ratio (TyG-WHtR) were calculated and categorized into quartiles. Cox proportional hazards models, restricted cubic splines, two-piecewise regression models, and K-means clustering were applied to evaluate the associations of TyG-related indices with CVD and mortality outcomes. Incremental predictive performance was further assessed using the net reclassification index (NRI) and integrated discrimination improvement (IDI).

resultsOver a median follow-up of 13.7 years, higher quartiles of TyG-BMI, TyG-WC, and TyG-WHtR were positively associated with all CVD outcomes. Among these indices, TyG-WC demonstrated the strongest associations, particularly for total CVD (hazard ratios [HRs] for the highest vs. lowest quartile: 1.42 [95% CI: 1.36-1.48]). For mortality outcomes, TyG-WC also exhibited the most pronounced associations, showing an HR of 1.51 (1.32-1.72) for CVD mortality. In contrast, the TyG index alone showed inverse associations with both CVD incidence and CVD mortality. Dose-response analyses revealed that TyG-related indices were linearly associated with coronary heart disease (CHD), whereas U- or J-shaped nonlinear relationships were observed for other CVD outcomes, with risks rising steadily beyond the identified inflection points. In predictive analyses, TyG-WC provided the greatest incremental predictive value for total CVD, all-cause mortality, and CVD mortality, while TyG-WHtR yielded the largest improvements for CHD and stroke. Moreover, results from trajectory analyses showed that participants with persistently high TyG-related trajectories had substantially elevated risks of CVD. All results remained robust across subgroup and sensitivity analyses.

conclusionsTyG-BMI, TyG-WC, and TyG-WHtR were robust predictors of CVD and mortality in individuals with MetS. These indices exhibited nonlinear threshold effects and improved predictive performance, supporting their utility in clinical risk stratification.